Research ArticleANTIBODIES

B cells engineered to express pathogen-specific antibodies protect against infection

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Science Immunology  17 May 2019:
Vol. 4, Issue 35, eaax0644
DOI: 10.1126/sciimmunol.aax0644

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B cells enter the cell therapy game

Antibodies are currently being used to treat a number of ailments from infectious diseases to cancers and autoimmunity. Like other drugs, patients often require multiple doses of antibodies. Because production and storage of antibodies are expensive, there has been considerable interest in finding alternative strategies to deliver antibodies. Here, Moffett et al. have engineered both human and murine B cells to express antibodies targeting a number of viruses, including respiratory syncytial virus (RSV), and report that a single injection of B cells expressing RSV-specific antibodies into mice lacking T and B to be protective. Their technology opens up the possibility of using engineered B cells as therapeutics.

Abstract

Effective vaccines inducing lifelong protection against many important infections such as respiratory syncytial virus (RSV), HIV, influenza virus, and Epstein-Barr virus (EBV) are not yet available despite decades of research. As an alternative to a protective vaccine, we developed a genetic engineering strategy in which CRISPR-Cas9 was used to replace endogenously encoded antibodies with antibodies targeting RSV, HIV, influenza virus, or EBV in primary human B cells. The engineered antibodies were expressed efficiently in primary B cells under the control of endogenous regulatory elements, which maintained normal antibody expression and secretion. Using engineered mouse B cells, we demonstrated that a single transfer of B cells engineered to express an antibody against RSV resulted in potent and durable protection against RSV infection in RAG1-deficient mice. This approach offers the opportunity to achieve sterilizing immunity against pathogens for which traditional vaccination has failed to induce or maintain protective antibody responses.

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